A Metabolism-Based Test to Diagnose Autism Spectrum Disorder and its Subtypes in Early Childhood

诊断儿童早期自闭症谱系障碍及其亚型的基于代谢的测试

• 批准号: 9126603
• 负责人: ROBERT E BURRIER
• 金额: $ 89.47万
• 依托单位: STEMINA BIOMARKER DISCOVERY, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-13 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9126603
• 关键词: 4 year old; Adherence; Age; Age-Months; Autistic Disorder; Behavior Therapy; Behavioral; Biochemical; Biochemical Pathway; Biological Markers; Blood; Child; Clinical; Clinical Research; Cognition; Communication; Computer Simulation; Coupling; Data; Data Set; Demographic Aging; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Diet; Disease; Early Diagnosis; Early treatment; Emotional; Enrollment; Family; Funding; Gender; Goals; Health; Individual; Institutional Review Boards; Link; Mass Spectrum Analysis; Measurement; Metabolic; Metabolism; Metadata; Methodology; Monitor; Multi-Institutional Clinical Trial; Patients; Phase; Physicians; Plasma; Preparation; Procedures; Reporting; Research; Resolution; Risk Assessment; Sampling; Sensitivity and Specificity; Services; Shipping; Ships; Social Functioning; Societies; Statistical Data Interpretation; Statistical Methods; Statistical Models; Symptoms; Syndrome; Testing; Training; United States; Urine; Work; Writing; autism spectrum disorder; base; behavior test; biomarker discovery; biomarker panel; blood-based biomarker; clinical biomarkers; clinical research site; cognitive function; data acquisition; diagnostic accuracy; early childhood; improved; improved outcome; individual patient; innovation; metabolic profile; metabolomics; new therapeutic target; novel; patient subsets; personalized medicine; repository; sample collection; segregation; social communication

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is now diagnosed in 1 of 68 children with recent reports citing as many as 1 in 50 children in the United States. The average age of diagnosis is more than 4 years. There is a need for a reliable biomarker-based test for earlier diagnosis of ASD in young children to improve outcomes such as cognition, social function and communication. This will subsequently decrease the financial and emotional burden on families and society. In 2012, Stemina began a self-funded Phase I equivalent study of plasma samples from nearly 400 ASD, Developmental Delay (DD) and Typically Developing (TD) children. From these studies, we developed computational models based on metabolic biomarker differences in ASD and TD children that could differentiate ASD from TD patients with an accuracy of about 80%. Stemina seeks funding to enroll 1500 patients in a well-defined clinical study to develop a biomarker-based diagnostic test capable of classifying ASD relative to other developmental delays at greater than 80% accuracy. In addition, we propose to identify metabolic subtypes present within the ASD spectrum that can be used for personalized treatment. The study will include ASD, DD and TD children between 18 and 48 months of age. Inclusion of DD patients is a novel and important aspect of this proposed study from the perspective of a commercially available diagnostic test. Our ultimate goals are to: (1) enable early diagnosis and treatment; (2) elucidate metabolic differences in subtypes of ASD patients to properly match the best available treatments for each patient from an individual biochemical perspective; and (3) identify biochemical alterations in patients across the spectrum that will provide targets for novel therapies. We will employ the innovative metabolomics approaches that we developed in Phase I, including coupling orthogonal chromatographic separation methodologies with both non- targeted and targeted high resolution mass spectrometry. Our study objectives will be to confirm biomarkers that were discovered in Phase I, expand those biomarker profiles for metabolic subtypes, and optimize the ASD test accuracy by creating panels of biomarker subtypes that will better describe this heterogeneous syndrome. Based on our Phase I data, we believe this clinical study will also allow us to confirm specific metabolic biomarkers of subtypes of ASD. This innovative approach to characterizing ASD will allow physicians to suggest the most appropriate treatment based on the individual metabolism of the patient.

 描述(由申请人提供)：目前68名儿童中有1人被诊断为自闭症谱系障碍(ASD)，最近的报告引用了多达50名美国儿童中的1人。平均确诊年龄4岁以上。需要一种可靠的基于生物标记物的测试来早期诊断幼儿ASD，以改善认知、社会功能和沟通等结果。这将随后减轻家庭和社会的经济和情感负担。2012年，Stemina开始对近400名ASD、发育迟缓(DD)和典型发育迟缓(TD)儿童的血浆样本进行自筹资金的I期相当研究。从这些研究中，我们开发了基于ASD和TD儿童代谢生物标志物差异的计算模型，该模型可以区分ASD和TD患者，准确率约为80%。Stemina寻求资金，在一项明确的临床研究中招募1500名患者，以开发一种基于生物标记物的诊断测试，能够以80%以上的准确率将ASD与其他发育迟缓进行分类。此外，我们建议确定ASD谱系中存在的可用于个性化治疗的代谢亚型。这项研究将包括18到48个月大的ASD、DD和TD儿童。从商业诊断试验的角度来看，纳入DD患者是这项拟议研究的一个新的和重要的方面。我们的最终目标是：(1)实现早期诊断和治疗；(2)阐明ASD患者亚型的代谢差异，以从个体生化角度正确匹配每个患者的最佳可用治疗；以及(3)识别各种患者的生化变化，为新疗法提供靶点。我们将采用我们在第一阶段开发的创新代谢组学方法，包括将正交色谱分离方法与非靶向和靶向高分辨率质谱学相结合。我们的研究目标将是确认在第一阶段发现的生物标记物，扩大这些代谢亚型的生物标记物谱，并通过创建将更好地描述这种异质性综合征的生物标记物亚型小组来优化ASD测试的准确性。基于我们的I期数据，我们相信这项临床研究也将使我们能够确认ASD亚型的特定代谢生物标记物。这种确定ASD特征的创新方法将使医生能够根据患者的个体新陈代谢提出最合适的治疗方案。